Title :

Activation of Nod2 signalling upon Norovirus infection enhances antiviral immunity and susceptibility to colitis

Author(s) :

Muharram, Ghaffar [Auteur correspondant]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Thépaut, Marion [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Lobert, Pierre-Emmanuel [Auteur]
Laboratoire de Virologie - ULR 3610 [Laboratoire de Virologie]
Grandjean, Teddy [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Boulard, Olivier [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Delacre, Myriam [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Wakeford, Emmrich [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Wheeler, Richard [Auteur]
Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall
POULIN, Lionel [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Gomperts Boneca, Ivo [Auteur]
Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall
Lafont, Frank [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Michallet, Marie-Cécile [Auteur]
Hober, Didier [Auteur]
Laboratoire de Virologie - ULR 3610 [Laboratoire de Virologie]
Cadwell, Ken [Auteur]
New York University School of Medicine [NYU Grossman School of Medicine]
Chamaillard, Mathias [Auteur correspondant]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]

Publication date :

2023-12-31

English keyword(s) :

NOD2
Norovirus
Inflammation
Colitis
Macrophages
Signalling

HAL domain(s) :

Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Maladies infectieuses
Sciences du Vivant [q-bio]/Immunologie/Immunité adaptative
Sciences du Vivant [q-bio]/Immunologie/Immunité innée
Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Hépatologie et Gastroentérologie
Sciences du Vivant [q-bio]/Microbiologie et Parasitologie/Virologie

English abstract : [en]

Over 90% of epidemic nonbacterial gastroenteritis are caused by human Noroviruses (NoV) which are persisting in a substantial subset of people allowing their spread worldwide. It leads to a significant number of endemic ...
Show more >Over 90% of epidemic nonbacterial gastroenteritis are caused by human Noroviruses (NoV) which are persisting in a substantial subset of people allowing their spread worldwide. It leads to a significant number of endemic cases and up to 70,000 children deaths in developing countries. NoVs are primarily transmitted through the fecal-oral route. To date studies have focused on the influence of the gut microbiota on viral clearance by enteric immunity. In this study, the use of the persistent mouse Norovirus S99 strain (MNoV_S99) allowed us to provide evidence that the norovirus-driven exacerbation of colitis severity relied on bacterial sensing by nucleotide-binding oligomerization domain 2 (Nod2). Similarly, another persistent MNoV_CR6 strain failed to exacerbate colitis severity in Nod2-deficient mice. In parallel, the viremia was heightened in these mice in comparison with control animals. Accordingly, a reduced level of phosphorylation of Signal Transducer and Activator of Transcription1 (STAT1) in Nod2-deficient macrophages infected by MNoV_S99 was measured. By contrast, STAT1 phosphorylation was increased in wild-type macrophages and associated with an induction of NOD2 expression. This in turn enhances myeloid cells response to muramyl dipeptide (MDP) resulting in downstream pro-inflammatory cytokine secretion and reduced noroviral production. Hence, our results uncover a previously unidentified virus-host-bacterial interplay that may represent a novel therapeutic target for treating noroviral origin gastroenteritis that may be linked with susceptibility to several common illnesses such as Crohn’s disease.Show less >

Language :

Anglais

ANR Project :

Integrative Biology of Emerging Infectious Diseases
LUMIERE
Modulation de l'activité du cerveau par le peptidoglycan bactérien

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Source :

Harvested from HAL